The FDA Reauthorization Act of 2017 (FDARA) created a new type of 180-day exclusivity for ANDA applicants applying for approval of certain drugs designated as Competitive Generic Therapies. The FDARA, according to FDA commissioner, Scott Gottlieb, “is part of our broader effort to foster generic competition and help address the high cost of drugs […] key step in making safe and effective generic drugs available to patients quickly and ensuring there’s adequate competition so patients have affordable access to the treatments they need.”

A drug can be designated as a Competitive Generic Therapy (CGT) if there is not more than one approved drug in the active section of the Orange Book. Applicants for drugs that receive a CGT designation receive review enhancements and expedited review of their Abbreviated New Drug Applications (ANDA) in addition to being eligible for a 180-day period of marketing exclusivity. Subparagraph (B)(v)(I) of FDARA sets forth the conditions under which this 180-day exclusivity blocks certain applications:

“[I]f the application is for a drug that is the same as a competitive generic therapy for which any first approved applicant has commenced commercial marketing, the application shall be made effective on the date that is 180 days after the date of the first commercial marketing of the competitive generic therapy (including the commercial marketing of the listed drug) by any first approved applicant.”

Under the Hatch-Waxman Act enacted in 1984, to amend the Federal Food, Drug and Cosmetic Act, an “applicant submitting the first application” was the applicant that submitted an application that was both (1) substantially complete and (2) contained a paragraph IV certification, prior to the submission of any other application for the same listed drug that was both substantially complete and contained the same certification.[1] The first generic applicant to file an ANDA containing a paragraph IV certification to a patent was eligible for 180 days of exclusivity, during which FDA could not approve a subsequent ANDA that challenged that patent for the same drug product.[2]

In 2003, the Medicare Prescription Drug, Improvement, and Modernization Act (“the MMA”) revised the 180-day exclusivity provisions of the Hatch-Waxman Amendments defining the term “First Applicant” as “an applicant that, on the first day on which a substantially complete application containing a [paragraph IV certification] is submitted for approval of a drug, submits a substantially complete application that contains . . . [a paragraph IV certification for the drug] and lawfully maintains a [paragraph IV certification] for the drug.”[3] The MMA also sets forth events under which a First Applicant would forfeit its eligibility for 180-day exclusivity, the events including (I) Failure to Market, (II) Withdrawal of Application, (III) Amendment of Certification, (IV) Failure to Obtain Tentative Approval, (V) Agreement with Another Applicant, the Listed Drug Holder, or a Patent Owner, and (VI) Expiration of All Patents.

On July 13, 2018, the FDA, in a letter to certain ANDA applicants, explained how it would determine the First Applicant under the MMA. Specifically, the FDA will no longer utilize the “First Effective” test in determining the First Applicant because doing so did not comply with the first prong of the MMA’s definition of First Applicant. The FDA highlighted that an applicant would be considered a “First Applicant” based on whether the applicant submitted a substantially complete ANDA with a paragraph IV certification[4] The pertinent portion of the letter reads:

“[A] “First Applicant” is “an applicant that, on the first day on which a substantially complete application containing a [paragraph IV certification] is submitted for approval of a drug, submits a substantially complete application that contains . . . [a paragraph IV certification for the drug] and lawfully maintains a [paragraph IV certification] for the drug.” Under the “First Submitted” interpretation, the definition of “First Applicant” is read such that the “when” prong (i.e., “on the first day on which a substantially complete application . . .”) refers to a single specific date on which an application was submitted to qualify its sponsor as a “First Applicant”; whereas the “submit” and “lawfully maintain” prongs describe requirements for specific applications submitted on this single fixed date to maintain eligibility for exclusivity. Under this reading of the statute, there can only ever be one “first day on which a substantially complete application containing a paragraph IV certification [or an amendment to a substantially complete application with a paragraph IV certification] is submitted,” regardless of whether the applicant that submits its application (or an amendment or supplement to its application) on that “first day” gives or fails to give timely notice of and/or otherwise lawfully maintains its paragraph IV certification. Thus, while an applicant must meet all three prongs to obtain 180-day exclusivity, the “when” prong refers to a specific, static date determined by the specific first day on which any applicant submits a substantially complete application (or an amendment or supplement to a substantially complete application) containing a paragraph IV certification to a patent listed for that product. This specific date is fixed and does not change because of subsequent events.”

The letter also addressed the timing to trigger the marketing forfeiture provision under Section 505(j)(5)(D)(i)(I), which provides that the 180-day exclusivity will be forfeited if the

“[F]irst applicant fails to market the drug by the later of (aa) the earlier of the date that is – (AA) 75 days after the date on which the approval of the application of the first applicant is made effective under subparagraph (B)(iii); or (BB) 30 months after the date of submission of the application of the first applicant; or (bb) with respect to the first applicant or any other applicant (which other applicant has received tentative approval), the date that is 75 days after the date as of which, as to each of the patents with respect to which the first applicant submitted and lawfully maintained a certification qualifying the first applicant for the 180-day exclusivity period under subparagraph (B)(iv), at least 1 of the following has occurred …”[5]

Addressing circumstances under which another applicant may trigger a forfeiture of the First Applicant’s 180-day exclusivity, the letter stated that the other applicant’s tentative approval can occur at any time prior to or after a subparagraph (bb) event occurs, as long as the tentative approval occurs by the time the FDA makes the forfeiture determination.

In a Complaint and Motion For a Preliminary Injunction filed by Teva Pharmaceuticals USA, Inc. on October 17, 2018 in the U.S. District Court for the District of Columbia, Teva alleged that FDA’s interpretation of the definition of “First Applicant” is unlawful. Teva asserted that it was the first generic applicant that complied with the Hatch-Waxman Act’s requirements for challenging at least one of the patents covering Restasis®. The facts, as alleged by Teva in the complaint, are as follows[6]:

On January 23, 2012, Teva submitted its cyclosporine ANDA to FDA with data and justification to demonstrate its product’s chemical equivalence and BE to Restasis®. Teva’s ANDA included a Paragraph III certification to the ‘979 patent, which by then was the only unexpired patent listed in the Orange Book.

At the time of Teva’s ANDA filing, FDA had not yet released any guidance recommending the tests ANDA applicants should perform or the standards they should satisfy in attempting to demonstrate BE to Restasis®.

On April 19, 2013 (more than a year after Teva submitted its ANDA), FDA requested additional information from Teva (the “IR”), nearly all of which, according to Teva, had been provided in its original ANDA.

On May 9, 2013 Teva submitted a formal response (A) identifying where the original ANDA included the requested information and (B) either re-providing or summarizing the information already contained in Teva’s ANDA.

While FDA was considering Teva’s Response, the Agency published its first draft BE guidance document for Restasis®-referencing ANDAs in June 2013. FDA then notified Teva (the “RTR Letter”) that it was refusing to file (or “receive”) the company’s ANDA because Teva’s January 2012 ANDA “ha[d] not demonstrated bioequivalence [to] the RLD” in accordance with the methods FDA recommended in its June 2013 Draft Guidance.

Teva stated that such guidance documents are not binding even when finalized, and that FDA’s review for substantial completeness is not intended to evaluate whether a submitted ANDA actually “demonstrated bioequivalence [to] the RLD…Instead, the relevant question is whether the submitted ANDA is facially sufficient – meaning that it makes a plausible effort to show BE[7]…FDA’s refusal even to receive Teva’s ANDA for review because it “has not demonstrated bioequivalence” violated that rule.”

Teva asserted that FDA’s RTR decision jeopardized Teva’s ability to qualify for 180-day exclusivity. Though Teva’s original ANDA had contained only a non-exclusivity-qualifying Paragraph III certification to the ‘979 patent, Allergan had filed a new Restasis®-related patent application with the PTO shortly after FDA issued its Letter and—while Teva was considering its response to RTR case—PTO announced that it would issue U.S. Patent No. 8,629,111 (“the ‘111 patent”) on January 14, 2014. Teva asserted that because it believed Allergan’s forthcoming patent was vulnerable to challenge, it naturally wanted to submit a Paragraph IV certification that could qualify it for exclusivity. However, Teva argued that, if it were forced to submit a new ANDA based on the June 2013 Draft Guidance and another applicant challenged the ‘111 patent in the interim, Teva would not be eligible for exclusivity.

Because Teva’s Paragraph IV certification was contained in an amendment to its previously-submitted-but-not-yet-received ANDA, the statute ordinarily would have required Teva to notify Allergan of its certification at the same time it submitted its amendment to FDA. But FDA consistently has held that applicants may not dispatch such notice until FDA receives first an ANDA for review; instead, FDA’s judicially affirmed rule is and has been that the legally-required notice will be considered timely-provided only (and so long as) it is dispatched within 20 days after FDA’s acknowledgement letter receiving a previously-submitted ANDA for review. Teva’s P-IV amendment therefore informed FDA that the company would send the legally required notice to Allergan and the ‘111 patentees once FDA reversed its RTR decision and received Teva’s ANDA for review.

On June 25, 2015 (some 29 months after Teva submitted its original ANDA to FDA), the Agency rescinded its RTR Letter—declaring that Teva’s ANDA in fact had been substantially complete from the outset and concluding “that ANDA 203880 may be received for review as of January 23, 2012 (i.e., the original submission date).” FDA subsequently issued a formal letter acknowledging the receipt of Teva’s ANDA, and Teva timely notified Allergan and the ‘111 patentees of its Paragraph IV certification. Allergan then sued Teva for infringing the ‘111 patent.

On July 28, 2015, FDA opened a docket regarding 180-day exclusivity for ANDAs referencing Restasis®. In particular, the Agency for the first time disclosed that at least one ANDA applicant had attempted to submit a Paragraph IV certification to the ‘979 patent before January 14, 2014 (i.e., the date Allergan listed the ‘111 patent in the Orange Book and Teva submitted its Paragraph IV certification), “[b]ut the ‘979 patent expired before FDA issued an Acknowledgement Letter to any applicant with a pending ANDA.” Because this so-called “‘979 Applicant” never notified Allergan of its certification before that patent expired, FDA asked cyclosporine ANDA applicants whether the ‘979 Applicant may have qualified for 180-day exclusivity despite failing to provide the legally-required notice.

Teva asserted that “[b]ecause the ‘979 Applicant(s) failed to provide a valid notice prior to the ‘979 patent’s expiration, any putative paragraph IV certification that the ‘979 Applicant(s) sent to FDA was incapable of grounding eligibility for exclusivity; it was a legal nullity given the absence of a valid notice.”

On October 6, 2016, FDA finalized its MMA-implementing regulations—expressly maintaining its proposed rule that eligibility for 180-day exclusivity hinges on the provision of a valid Paragraph IV notice to the brand manufacturer. With FDA having made clear that the ‘979 Applicant could not have qualified for 180-day exclusivity, and thus that Teva had qualified for 180-day exclusivity by virtue of its Paragraph IV certification to the ‘111 patent, Teva prioritized its cyclosporine ANDA with the aim of launching the product, with exclusivity, at the earliest opportunity. On October 16, 2017, Teva won its patent litigation with Allergan—securing a district court decision declaring Allergan’s asserted patents to be invalid and thereby opening the market to competition years before those patents were set to expire.

On July 13, 2018, FDA issued a letter decision in another matter[8] holding that ANDA applicants can qualify for 180-day exclusivity even if they never provide the brand manufacturer with the legally required notice of a putative Paragraph IV certification.

According to Teva’s complaint:

“Until now, FDA consistently maintained that eligibility for 180-day exclusivity hinges on a generic applicant submitting a legally valid challenge to the innovator’s patents that complies with all statutory requirements for such challenges—including the requirement to notify the brand manufacturer of any such challenge so that it can evaluate whether to sue the generic applicant for patent infringement…And while this case arises under a more recent version of the statute, FDA recently promulgated binding regulations—after formal notice-and-comment rulemaking—that not only affirmed its longstanding position, but expressly relied on the court cases upholding that well-settled rule[9]…FDA’s attempt to jettison that rule in the context of a quasi-adjudicatory proceeding is thus as procedurally defective as it is substantively baffling.”

Teva is seeking declaratory and injunctive relief, including (i) a declaration that “FDA’s Letter Decision conflicts with the plain text, broader incentive structure, and legislative intent of the FDCA and therefore is “arbitrary, capricious, an abuse of discretion of otherwise not in accordance with law,” a declaration that Teva’s Restasis®-referencing ANDA No. 203880 is entitled to 180-day exclusivity, and that the court enjoin FDA from approving any ANDA for generic Restatsis® that “was not substantially complete as of January 14, 2014 and/or for which the ANDA’s sponsor did not submit a lawfully-maintained Paragraph IV certification on January 14, 2014.”

[4] Timely notice of its ANDA filing to the brand is no longer required for an applicant to be qualified as a First Applicant. Nevertheless, First Applicants must continue to provide timely notice of its ANDA to the brand to qualify for the 180-day exclusivity.

[5] “(AA) In an infringement action brought against that applicant with respect to the patent or in a declaratory judgment action brought by that applicant with respect to the patent, a court enters a final decision from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the patent is invalid or not infringed. (BB) In an infringement action or a declaratory judgment action described in subitem (AA), a court signs a settlement order or consent decree that enters a final judgment that includes a finding that the patent is invalid or not infringed. (CC) The patent information submitted under subsection (b) or (c) is withdrawn by the holder of the application approved under subsection (b).”

[7] This assessment [for substantial completeness] does not involve evaluating whether the data and information in the ANDA are in fact sufficient to demonstrate that the [ANDA] meets a requirement for approval, such as bioequivalence. Rather, the assessment involves evaluating whether the data and information in the ANDA are the types of data and information that could plausibly support an approval action and hence merit further review by the Agency. FDA Docket No. 2015-P-0065-0027, at 39 (Feb. 10, 2016) (emphasis added); see also 21 C.F.R § 314.101(d)(3) (allowing FDA to refuse to receive an ANDA only if “it does not on its face contain information required”) (emphasis added).

[8] There, as here, a generic applicant submitted a Paragraph IV certification to a listed patent before any other applicant had done so, but never provided the brand manufacturer with notice of its putative Paragraph IV certification. In addressing whether that applicant nonetheless qualified for 180-day exclusivity, FDA initially conceded that its MMA regulations expressly maintained the Agency’s longstanding position that eligibility for 180-day exclusivity requires timely notice of the exclusivity-qualifying Paragraph IV certification. But FDA quickly dismissed that fact on the ground that the MMA regulations principally addressed cases in which a Paragraph IV certification was submitted via amendment to an ANDA rather than in an original ANDA even though exclusivity can be awarded only to a “first applicant,” even though the MMA defines “first applicant” without regard to whether the potentially-exclusivity qualifying certification is contained in an original ANDA or submitted via amendment, and even though the Agency’s decision went on to adopt the same rule for both amended ANDAs and original ANDAs. On the merits, FDA asserted that its new rule was more consistent with the statute’s language than its duly-promulgated MMA regulations because the MMA’s definition of “first applicant” allegedly provides that there can only ever be one “first day on which a substantially complete application containing a paragraph IV certification … is submitted,” regardless of whether the applicant that submits its application (or an amendment or supplement to its application) on that “first day” gives or fails to give timely notice of and/or otherwise lawfully maintains its paragraph IV certification. FDA further asserted that its new rule was more “consistent with the structure of the MMA” because the statute elsewhere provides that 180-day exclusivity does not “roll” to a subsequent applicant after the “first applicant” loses its eligibility for 180-day exclusivity.

[9] Abbreviated New Drug Applications and 505(b)(2) Applications—Final Rule (the “MMA Final Rule”), 81 Fed Reg. 69580, 69609 (Oct. 6, 2016) (adopting proposed rule that applicants must “satisfy the notice requirement of the [Hatch-Waxman] Act … to qualify for 180-day exclusivity”); see also Abbreviated New Drug Applications and 505(b)(2) Applications—Proposed Rule (the “MMA Proposed Rule”), 80 Fed. Reg. 6802, 6835 (Feb. 6, 2015) (citing Purepac to support proposal that a patent challenge is “effective only as of the date that the applicant has both submitted … the paragraph IV certification and sent the notice”).

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